Cystathionine γ-lyase protects against renal ischemia/reperfusion by modulating oxidative stress

Eelke M. Bos, Rui Wang*, Pauline M. Snijder, Miriam Boersema, Jeffrey Damman, Ming Fu, Jill Moser, Jan Luuk Hillebrands, Rutger J. Ploeg, Guangdong Yang, Henri G.D. Leuvenink, Harry Van Goor

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

170 Citations (Scopus)

Abstract

Hydrogen sulfide (H2S) is an endogenous gasotransmitter with physiologic functions similar to nitric oxide and carbonmonoxide. Exogenous treatment with H2S can induce a reversible hypometabolic state, which can protect organs from ischemia/reperfusion injury, but whether cystathionine γ-lyase (CSE), which produces endogenous H2S, has similar protective effects is unknown. Here, human renal tissue revealed abundant expression of CSE, localized to glomeruli and the tubulointerstitium. Compared with wild-type mice, CSE knockout mice had markedly reduced renal production of H2S, and CSE deficiency associated with increased damage and mortality after renal ischemia/reperfusion injury. Treatment with exogenous H2S rescued CSE knockout mice from the injury and mortality associated with renal ischemia. In addition, overexpression of CSE in vitro reduced the amount of reactive oxygen species produced during stress. Last, the level of renal CSE mRNA at the time of organ procurement positively associated with GFR 14 days after transplantation. In summary, these results suggest that CSE protects against renal ischemia/reperfusion injury, likely by modulating oxidative stress through the production of H2S.

Original languageEnglish
Pages (from-to)759-770
Number of pages12
JournalJournal of the American Society of Nephrology
Volume24
Issue number5
DOIs
Publication statusPublished - 30 Apr 2013
Externally publishedYes

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